NZ236514A

NZ236514A - Use of a chlorine dioxide solution to disinfect contact lenses

Info

Publication number: NZ236514A
Application number: NZ236514A
Authority: NZ
Inventors: Anthony J Dziabo; Hampar Karageozian; Paul S Ripley
Original assignee: Allergan Inc
Priority date: 1990-01-05
Filing date: 1990-12-18
Publication date: 1992-12-23
Also published as: PH27046A; IE910031A1; WO1991009632A1; US4997626A; AU7163591A; PT96432A; HU9202224D0; AU640740B2; EP0507837A4; IL96785A0; HUT61669A; CA2070282A1; EP0507837A1; US5135623A; BR9007958A; ZA9171B; JPH05502812A

Description

<div class="application article clearfix" id="description"> New Zealand Paient Spedficaiion for Paient Number £36514 c 236514 I CofriH**** Sr^;•'.?.• v.i>.-'S •';•• | cw: 2 3 DEC 1992 - ::*v-iU ............7......'P.Yfr ' ■•■: j 9ft* * ** « m] in *'■ * ; . -1 ",2' ^ i '* j S.Mf' f> me ^ "METHODS TO DISINFECT CONTACT LENSES" XK/We, ALLERGAN, INC., a Corporation organized under the laws of the State of Delaware, one of the United States of America, of 2525 Dupont Drive, Irvine, California 92713-9534, United States of America. hereby declare the invention for which XiX/j? we pray that a patent may be granted to and the method by which it is to be performed, to be particularly described in and by the following statement: - _ 1 _ (followed by page la) 236 5 \Q METHODS TO DISINFECT CONTACT LENSEfc- BACKGROUND OF THE INVENTION This invention relates to disinfecting lenses, such as contact lenses. In particular, the invention relates to methods useful to quickly and effectively disinfect contact lenses. Contact lenses should be periodically disinfected to protect the wearer's eyes from infection and to improve the wearer's comfort. It is often desirable that lens disinfecting be accomplished quickly, e.g., for the convenience of the wearer. However, conventional fast-acting disinfectants that are used with contact lenses have a high potential to cause eye irritation. A disinfectant which can be easily and effectively dissipated after use would be advantageous to reduce the chance of eye irritation. Stockel et al U.S. Patent 4,499,077 discloses an antimicrobial composition for soft contact lenses including an oxidizing agent such as an oxyhalogen compound, e.g., stabilized chlorine dioxide, or hydrogen peroxide, and a polymeric germicide, e.g., a quaternary ammonium polymer or an amino and/or imino polymer or salts thereof. Stockel et al U.S. Patent 4,654,208 discloses an antimicrobial composition for contact lenses including an aqueous solution of a germicidal polymeric nitrogen compound and an oxidizing agent, e.g., chlorine dioxide, stabilized chlorine dioxide or hydrogen peroxide, to potentiate the activity of the germicidal polymeric nitrogen compound at low concentrations. The Stockel et al patents characterize the "polymeric germicides" and the "germicidal polymeric nitrogen compounds" as positively charged, nitrogen-containing cationic polymers, such as certain quaternary ammonium polymers and polymeric amino and/or imino compounds, e.g., polydiguanides. Neither of these Stockel et al patents relate to contact lens 236 5 1 4 2 disinfecting compositions without such positively charged, nitrogen-containing cationic polymers. In addition to being disinfected, the contact lens should be cleaned, e.g., of protein-based debris which accumulates on the lens during use. Such lens cleaning is often done in the presence of one or more enzymes. See, for example, Karageozian U.S. Patent 3,910,296. In many instances, a complete lens maintenance procedure involves first enzymatic cleaning followed by a separate lens disinfecting step. SUMMARY OF THE INVENTION New methods for disinfecting, and preferably cleaning, lenses, in particular contact lenses, have been discovered. These methods utilize an amount of chlorine dioxide effective to disinfect the lens. Chlorine dioxide has been found to be a very effective contact lens disinfectant. The chlorine dioxide is effective as a contact lens disinfectant without requiring the presence of other germicides. Thus, chlorine dioxide can be the sole contact lens disinfectant. In addition, after the desired disinfecting has taken place, the contact lens can be effectively freed, e.g., by rinsing, neutralization, etc., of residual chlorine' dioxide so as to reduce the chances of eye irritation when the disinfected contact lens is placed in the eye. In one broad aspect, the invention involves a method for disinfecting a lens, e.g., a contact lens. A lens to be disinfected is contacted in a liquid medium with chlorine dioxide present in an amount effective to disinfect the lens to be disinfected. The liquid medium is substantially free of quaternary ammonium salts and positively charged, nitrogen-containing cationic polymers, such as those discussed in the above-noted Stockel et al patents. This contacting results in the lens being disinfected. After disinfection, the disinfected lens may be placed directly in the eye. Alternately, a simple saline rinse and/or soak of the 2365 14 3 disinfected lens may be employed before placing the lens in the eye. In another broad aspect of the invention, the disinfected contact lens or the contact lens to be disinfected is contacted with at least one enzyme capable of removing protein-based debris from a contact lens in an amount effective to remove protein-based debris from the disinfected contact lens or the contact lens to be disinfected. This removal or cleaning step is preferably conducted before the disinfecting step. Overall, the present invention is very effective and easy to use. This encourages the lens wearer to disinfect, and preferably clean, his/her contact lenses frequently, resulting in more comfort and less eye irritation. DETAILED DESCRIPTION OF THE INVENTION The present system is applicable for disinfecting all types of lenses, e.g., contact lenses, which are benefited by periodical disinfecting. Such lenses may be made of any material or combination of materials and may have any suitable configuration. One important feature of the present invention is the use of chlorine dioxide per se as the lens disinfectant. Preferably, the disinfecting is performed by chlorine dioxide in a liquid medium. Thus, chlorine dioxide itself may be dissolved in the liquid medium and used to disinfect the lens. However, it is often impractical or even impossible to dissolve sufficient gaseous chlorine dioxide in a liquid medium, e.g., saline, to be an effective contact lens disinfectant. In addition, the dissolved chlorine dioxide is often very rapidly lost from the liquid medium. In order to avoid these concerns, the liquid medium may, and preferably does, initially include at least one "precursor" of chlorine dioxide. Such precursors act in the liquid medium in response to one or more factors other than 23 6 5 4 the presence of the lens to be disinfected to produce chlorine dioxide in a lens disinfecting amount. Chlorine dioxide per se and not, for example, a chlorine dioxide precursor, acts as the primary, preferably as the sole, disinfecting agent to disinfect the lens. As used herein, a disinfecting amount of chlorine dioxide means such amount as will reduce the microbial burden or load by one log order in 3 hours or less, preferably in 1 hour or less, and more preferably in 10 minutes or less. The liquid medium is substantially free of any quaternary ammonium salts, and positively charged, nitrogen-containing cationic polymers, such as those disclosed as having antimicrobial or germicidal properties in the above-noted Stockel et al patents. Among the positively charged, nitrogen-containing cationic polymers which have antimicrobial or germicidal properties are quaternary ammonium polymers, such as copolymers of at least one mono-or di-functional tertiary amine and a dihalo organic compound. Also included in such positively charged, nitrogen-containing cationic polymers are polymeric amino and/or imino compounds, such as polydiguanides. Preferably, the liquid medium, in particular the liquid aqueous medium, used in the present chlorine dioxide contacting step is substantially free of any and all antimicrobial agents (meaning to include therein germicides) other than chlorine dioxide and one or more precursors of chlorine dioxide. As used herein, the term "antimicrobial agent" means a material which when included in liquid water at a concentration similar to the concentration of known effective, non-oxidative contact lens disinfectants in aqueous contact lens disinfecting solutions, for example at a concentration of 0.6% by weight or less, or even at a concentration of 0.2% by weight or less, is itself an effective contact lens disinfectant, i.e., is effective to 365 n 5 reduce the microbial burden or load by one log order in 3 hours or less, preferably in 1 hour or less, and more preferably in 10 minutes or less. In general, the chlorine dioxide precursors useful in the present invention are those which form or produce chlorine dioxide in a liquid medium, preferably a liquid aqueous medium, in response to at least one factor other than the presence of the lens to be disinfected. For example, such chlorine dioxide precursors may form' or produce chlorine dioxide in the presence of certain metal-containing components or in a reduced pH environment. The use of metal containing-components to promote chlorine dioxide formation from chlorine dioxide precursors is more fully described in U.S. Patent No. 5,078,908 issued January 7, 1992. The use of reduced pH to activate chlorine dioxide precursors to produce chlorine dioxide is more fully described in New Zealand Patent Specification No. 236513. Each of this patent and this application is incorporated in its entirety by reference herein. Among the preferred chlorine dioxide precursors useful in the present invention is stabilized chlorine dioxide. The exact chemical composition of many of the chlorine dioxide precursors, e.g., stabilized chlorine dioxide, is not completely understood. The manufacture or production of certain chlorine dioxide precursors is described in McNicholas U.S. Patent 3,27 8,447, which is hereby incorporated in its entirety by reference herein. An especially useful chlorine dioxide precursor source is a product sold under the trademark Purogene by Bio-Cide International, Inc. The chlorine dioxide precursor may be included in a liquid medium at a predetermined concentration, e.g., a concentration chosen to provide a 2365 6 disinfecting amount of chlorine dioxide in response to at least one factor other than the presence of the lens to be disinfected. Preferably, the liquid medium has sufficient chlorine dioxide precursor so as to have a potential of producing chlorine dioxide in the range of about 0.002% to about 3% by weight, based on the total weight of the liquid medium including the chlorine dioxide precursor or precursors. In one embodiment, the chlorine dioxide precursor includes a functionality selected from carbonate, borate, sulfate, phosphate, and mixtures thereof. The liquid medium used is selected to have no substantial detrimental effect on the lens being treated and to allow, and preferably to even facilitate, the present lens treatment or treatments. The liquid medium is preferably aqueous-based. A particularly useful liquid aqueous medium is that derived from saline, e.g., a conventional saline solution. 2365 14 7 The disinfecting contacting preferably occurs at a temperature to maintain the liquid medium substantially liquid. For example, when the liquid medium is aqueous-based, it is preferred that the contacting temperature be in the range of about 0° C. to about 100° C., and more preferably in the range of about 10° C. to about 60° C. Contacting at or about ambient temperature is very convenient and useful. The contacting preferably occurs at or about atmospheric pressure. This contacting preferably occurs for a time to substantially completely disinfect the lens being treated. Such contacting times can be in the range of about 0.1 hours to about 12 hours or more. In order to insure that the pH of the liquid aqueous medium is maintained within the desired range during the disinfecting procedure, the liquid aqueous medium may include at least one buffer component. Although any suitable buffer component may be employed, if a chlorine dioxide precursor is employed it is preferred to select such component so as not to substantially detrimentally affect the desired formation of chlorine dioxide. It is preferred that the buffer component be inorganic. Among the preferred buffer components are those which include phosphate functionalities, borate functionalities, carbonate functionalities and mixtures thereof. Particularly increased rates of chlorine dioxide formation are achieved when the buffer component includes phosphate functionalities, borate functionalities and mixtures thereof. Alkali metal and alkaline earth metal buffer components are advantageously used in the present invention. In one embodiment, the lens is subjected to the action of at least one enzyme to remove debris in addition to disinfecting the lens. This enzyme/lens contacting occurs in a liquid medium, preferably an aqueous liquid medium, such as described elsewhere herein. Among the types of debris that 236 5 1 4 8 form on contact lens during normal use are protein-based debris, mucin-based debris, lipid-based debris and carbohydrate-based debris. One or more types of debris may be present on a single contact lens. The enzyme or enzymes used are capable of removing at least one type of debris from a contact lens. The amount of such enzyme or enzymes used is effective to remove substantially all of at least one type of debris from a debris laden contact lens in a reasonable time, preferably in the range of about l minute to about 12 hours. The active enzyme-containing liquid medium preferably contains sufficient enzyme to provide between about 0.0001 to about 5 Anson units of activity, more preferably between about 0.01 to about 1 Anson units, per single lens treatment. The enzyme employed may be selected from enzymes which are conventionally employed in the enzymatic cleaning of contact lenses. For example, many of the enzymes disclosed in Huth et al Reissue U.S. Patent 32,672 are useful in the present invention. This patent is incorporated in its entirety by reference herein. Among the useful enzymes are those selected from proteolytic enzymes, lipases and mixtures thereof. The enzyme may be one or more carbohydrate-active enzymes. Specific examples of useful enzymes include proteases, amylases, lipases and mixtures thereof. The cleaning action of the enzyme may occur prior to or after the chlorine dioxide disinfecting of the lens. In one embodiment, the liquid medium which includes the chlorine dioxide precursor also includes the enzyme. If the precursor is present during the enzyme cleaning, the precursor should be maintained so that substantially no chlorine dioxide is formed. After sufficient time for effective enzymatic cleaning of the lens has elapsed, the precursor is promoted, activated or otherwise induced to produce chlorine dioxide to 236 5 14 9 disinfect the enzymatically cleaned lens. Alternately, the enzyme can be present in a delayed release form together with a chlorine dioxide neutralizing component, e.g., an acidity adjusting component such as a basic or buffer component. In this embodiment, the enzyme is released after the lens in disinfected. Thus, the enzyme is released at substantially the same time or after the chlorine dioxide neutralizing component and acts to clean the disinfected lens with no substantial interference from chlorine dioxide. The following non-limiting examples illustrate certain aspects of the present invention. EXAMPLE 1 This example illustrates the effect of stabilized chlorine dioxide concentration on the production of chlorine dioxide. A series of solutions was prepared using different concentrations of a stabilized chlorine dioxide product, sold by Bio-cide International, Inc. under the trademark Purogene. The stabilized chlorine dioxide product included 2.0% by weight of potential (ultimate yield) chlorine dioxide and 0.085% by weight of sodium carbonate. Each of these solutions was prepared as follows: (1) 0.1% (W/V) of boric acid was dissolved in deionized water to provide buffering; (2) a calculated amount of sodium chloride was added so that the final solution was isotonic; (3) the pH of the solution was adjusted to 7.5; (4) the desired amount of the stabilized chlorine dioxide product was added; and (5) the final volume of the solution was adjusted using deionized water. Each of these solutions was tested as follows. A 10 ml. sample of the solution was placed in a plastic container at ambient temperature and pressure. A plastic disc, containing 23 6 5 1 10 platinum as platinum oxide, was placed in the container in the solution. The actual concentration of chlorine dioxide in the solution was monitored at various times after the disc was placed in the container. Results of these tests were as follows: TABLE 1 Stabilized CIO?! Product Concentrations, ppm. bv wt. Time 0.0 50 100 250 500 750 1000 (min) C102 Concentration, ppm. by wt. 0 0.0 0.00 0.00 0.00 0.00 0.00 0.00 30 0.0 0.74 0.99 1.80 3.76 6.40 6.31 60 0.0 0.94 1.61 5.11 6.11 8.19 10.79 90 0.0 1.09 1.66 3.72 10.93 8.46 12.28 120 0.0 0.90 1.81 4.06 12.08 11.80 12.78 240 0.0 1.13 1.26 4.95 8.10 11.18 19.19 480 0.0 1.00 1.28 4.08 5.17 10.23 13.78 These results indicate that the concentration of chlorine dioxide reaches a maximum and then begins to decrease with time. Further, the initial pH of each solution was about 7.5 and remained substantially unchanged throughout the test. It has been reported that essentially no chlorine dioxide was detected in a borate buffered, 0.85% sodium chloride aqueous solution containing the above-noted stabilized chlorine dioxide product at a pH of 7.5. Thus, these results do demonstrate that platinum does effect formation of chlorine dioxide. EXAMPLE 2 A solution containing deionized water, 0.85% (w/v) of sodium chloride, 0.10% (w/v) of boric acid, and 50 ppm w/v of the stabilized chlorine dioxide product identified in Example 1 was prepared. Each of the concentrations of stabilized chlorine dioxide product set forth in Examples 2 and 3 is stated in terms of potential chlorine dioxide. One portion of this solution was buffered to a pH of 7.9, while the other 23 6 5 1 ii portion was buffered to a pH of 6.8. Varying amounts of tartaric acid was added to different samples of each of these portions. The samples were then tested, following the standard procedure, to determine the D-value with respect to various microorganisms. The D-value is defined as the length of time required to reduce the microbial burden or load by one log unit. Results of these tests were as follows: TABLE 2 pH = 6.8 Tartaric Acid, ppm. 30 40 50 60 70 Free Chlorine Dioxide, ppm. 10.74 17.08 37.94 25. 38 32.47 Microorganism Extrapolated D- •value at 23° C. , min. S. marcescens <.84 <.84 < .84 <.84 <.84 S. aureus <.87 <.87 <.87 < .87 <.87 P. aeruginosa <.85 <.85 <.85 <.85 <.85 A. fumigatus <.83 < .83 <.83 <183 <.83 pH = 7.9 Tartaric Acid, ppm. 30 40 50 60 70 Free Chloride Dioxide, ppm. 0.03 0.11 0.05 0.15 0.23 Microorganism Extrapolated D- -value at 23° C. , min. S. marcescens 5.13 <.85 2.56 <.85 2.56 S. aureus 10.17 2.54 2.54 12.24 2.54 P. aeruginosa 19.48 <.87 2.6 <.87 < .87 A. fumigatus 109 109 150 162 .270.6 These results of Examples 1 and 2 indicate that chlorine dioxide per se can be present in a sufficient amount in a liquid medium to be effective to disinfect contact lenses. 23 6 5 14 r*. 12 Thus, these results demonstrate that sufficient chlorine dioxide can be provided in a liquid medium to reduce the microbial burden or load by one log order in a period of time generally deemed acceptable for disinfecting contact 5 lenses. EXAMPLE 3 A lens disinfecting system was provided which included a solution, an activator tablet and a neutralizer tablet. The solution was purified water with the following 10 components: 0.85% (w/v) sodium chloride; 0.10% (w/v) boric acid; and 0.005% (w/v) the stabilized chlorine dioxide product identified in Example 1. The pH of this solution is about 7.7 to 7.9. The activator tablet had the following composition: 27.0 ',5 mg. tartaric acid; 10.0 mg. anhydrous sodium carbonate; 40.6 mg. sugar-based binder/filler; and 2.4 mg. polyethylene glycol (molecular weight of about 3350) (a conventional tableting lubricant). The neutralizer tablet had the following composition: ) 3.0 mg. tartaric acid; 21.0 mg. sodium carbonate; 23.3 mg. sugar-based binder/filler; 1.5 mg. polyethylene glycol (molecular weight of about 3 350); and 1.2 mg. N-acetylcysteine. The activator tablet was placed in 10 ml. of the solution ; and the resulting material was monitored for pH and chlorine dioxide concentration. Chlorine dioxide appeared in 28 + 3 seconds. The pH of the material was noted at 3.6 + 0.1. After 5 minutes, the chlorine dioxide concentration was 43.62 + 0.38 ppm. After 30 minutes, the chlorine dioxide concentration was 41.12 + 0.92 ppm. The neutralizer tablet was then placed in the material. The neutralizer tablet dissolved in the material. Upon shaking the material, the characteristic color of chlorine dioxide which was present disappeared immediately. The pH of </div>

Claims

<div class="application article clearfix printTableText" id="claims"> 236 r> 11 the final solution was 6.61 + 0.03 and drifted up to about 7 after 30 minutes. The chlorine dioxide concentration of the final solution is 0.16 + 0.04 ppm. The amount of chlorine dioxide produced by combining the 5 activator tablet with the solution is effective to kill most microorganisms in about 10 minutes or less, e.g., about 1 to 2 minutes. Disinfection of soft contact lens can be accomplished in about 1 to 2 minutes. However, at this point, the solution has a disagreeable odor and color, a low pH and 10 may contain sufficient chlorine dioxide to cause eye irritation. The neutralizer tablet is added to the solution to raise the pH to a comfortable level and consume chlorine dioxide. A disinfected contact lens could be taken from the neutralized 15 system and placed directly in the eye without irritation or discomfort. Alternately, the disinfected contact lens could be removed from the chlorine dioxide-containing solution and contacted, e.g., washed, with a buffered saline solution prior to being placed into the eye. While this invention has been described with respect to various specific examples and embodiments, it is to be understood that the invention is not limited thereto and that it can be variously practiced within the scope of the following claims. ) 236514 14 WHAT WE CLAIM IS:

1. A method for disinfecting a contact lens """*) which comprises: contacting a contact lens in a liquid medium with chlorine dioxide, as other than a chlorine dioxide precursor, present in an amount effective to disinfect said contact lens and thereby effectively disinfecting said contact lens, said liquid medium being substantially free of quaternary ammonium salts and positively charged, nitrogen-containing cationic polymers and including stabilized chlorine dioxide prior to said contacting.

2. The method of claim 1 wherein said liquid medium is an aqueous liquid medium which is substantially free of any antimicrobial agent other than chlorine dioxide and one or more precursors of chlorine dioxide.

3. The method of claim 1 or 2 wherein said liquid medium includes at least one buffer component.

4. The method of any of claims 1, 2 and 3 which further comprises contacting said contact lens with at least one enzyme capable of removing debris from a contact lens in an amount effective to substantially remove at least one type of debris from said contact lens.

5. The method of claim 4 wherein each of said at least one enzyme is selected from the group consisting of proteolytic enzymes, lipases and carbohydrate-active enzymes. 15

6. A method for disinfecting a contact lens which comprises: contacting a contact lens in a liquid medium with chlorine dioxide present in an amount effective to disinfect said contact lens, said chlorine dioxide being derived from stabilized chlorine dioxide present in said liquid medium prior to said contacting, wherein said stabilized chlorine dioxide is activated other than by the presence of said contact lens to produce said chlorine dioxide, said liquid medium being substantially free of quaternary ammonium salts and positively charged, nitrogen-containing cationic polymers.

7. The method of claim 6 wherein said liquid medium is an aqueous liquid medium which is substantially free of any antimicrobial agent other than chlorine dioxide and one or more precursors of chlorine dioxide.

8. The method of claim 6 or 7 wherein said liquid medium includes at least one buffer component,

9. The method of any of claims 6, 7 and 8 which further comprises contacting said contact lens with at least one enzyme capable of removing debris from a contact lens in an amount effective to substantially remove at least one type of debris from said contact lens.

10. The method of claim 9 wherein each of said at least one enzyme is selected from the group consisting of proteolytic enzymes, lipases and carbohydrate-active enzymes. V £ i 236514 16

11. The method of claim 9 or 10 wherein said at least one enzyme contacting occurs in a liquid medium including said chlorine dioxide precursor.

12. The method of claim 9 or 10 wherein said at least one enzyme contacting occurs in a liquid medium in the substantial absence of said chlorine dioxide precursor.

13. A method for disinfecting a contact-lens as defined in claim 1 or claim 6 substantially as herein described with reference to any example thereof. N.Z. PAT'"'1'" C'—'CB 11 SEP 1832 </div>